During the period of our ongoing study we have published results demonstrating the existence of a characteristic replicable and persistent profile of quantitative EEG (QEEG) abnormalities associated with long-term cocaine dependence. Electrophysiological heterogeneity (QEEG subtypes) existed at baseline, independent of length of exposure to cocaine, but significantly related to length of stay in treatment (continued abstinence). Significant interactions between subtype membership, comorbidity and gender were found to exist. An electrophysiological database has been constructed containing EEG, EP, neuropsychological, demographic and clinical data, collected from 452 evaluations from 149 subjects, at baseline and follow-up intervals of up to 18 months sustained abstinence. Preliminary study has revealed that some QEEG features persist while others move toward normal with sustained abstinence. Normalization, when it occurred, was at different rates for different QEEG features and significantly interacted with gender. This renewal application has been designed to examine the implications and significance of the results of the previous years of study, and will allow us to: [11 identify the specific features of the QEEG profile which remain abnormal in the chronic cocaine users during prolonged abstinence, and to study the incidence of such features in order to determine whether these are 'traits present prior to initiation of cocaine use or develop with chronic exposure. We hypothesize that the delta deficit in frontal cortex found in all subtypes may be such a 'trait, reflecting decreased activity of delta generating neurons in lower cortical layers as a consequence of decreased dopaminergic thalamo-cortical drive and predict that it will appear with high incidence in non-drug using siblings; [2] identify the specific features of the QEEG profile which reflect an abnormal 'state', becoming more normal with prolonged abstinence, and predict that it will not display higher incidence in non-using siblings. We hypothesize that the global alpha excess is such a feature, probably reflecting decreased ascending reticular activation of thalamo-cortical interactions, as a consequence of either deficient serotonergic transmission or striatal-nigral inhibition, and that it will gradually normalize during prolonged abstinence; [3] determine whether gender significantly interacts with change of abnormal features with sustained abstinence; [4] determine if additional features become more normal with confirmed abstinence extending to 24 months. Application of new mathematical algorithms will permit identification of the most probable neuroanatomical sources generating the QEEG, which may improve understanding of underlying mechanisms and help target new medications.